EU Directive 2001/83/EC
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Transcript of EU Directive 2001/83/EC
EU Directive 2001/83/EC
Dr. P. V. Appaji, M.Pharm, Ph.D
Director General,PHARMACEUTICALS EXPORT PROMOTION COUNCIL OF INDIA
HyderabadEmail: [email protected]
Presentation by
CONTENTSWhich are EU Countries?Objectives of EU Directive 2001/83/ECDefinition of Falsified Medicinal ProductPotential targets of EU Directive 2001/83/ECCurrent Indian Pharmaceutical Industry StatusAdvantages with EU Directive to IndiaDisadvantages with EU Directive to IndiaPossible Negotiations
Which Are EU Countries?
Objectives Of EU Directive 2001/83/EC
Introduction of a New Term Falsified Medicinal Product
Aims to prevent suspected medicines reaching patients
Safety features to be harmonised within the Union
Aims safety measures All through the supply chain (manufacturer to end user)
Contd…
Prevent distortions in the internal market
Prevent falsified medicinal products entering the legal supply chain
Aims at Ensuring Good Manufacturing Process of EU/EU Pharmacopoeia standards
Aims at Pharmaceutical product quality for APIs, Generics formulations, Excipients at the manufacturing level
Objectives Of EU Directive 2001/83/EC
EU Defines Falsified Medicine AsAny medicinal product with a false representation of:
a. Its identity, inclusive of package and labeling, its name or its composition as regards to any of the ingredients inclusive of excipients and the strength of those ingredients;
b. Its source, its manufacture, its country of manufacturing, its country of origin or its marketing authorisation holder;
c. Its history: The records and documents relating to the distribution channels used
The definition Excludes unintentional quality defects and is without prejudice to infringements of intellectual property rights
Potential Targets Of EU Directive 2001/83/EC
Confirming GMP with audits (for APIs, formulations, Excipients)
Confirming distribution with audits
Confirming GMP practices at least equivalent to those laid down by the Union
Notification to the authority for any changes that may impact on the quality or safety of the active substances that are manufactured, imported or distributed
Contd…
Implementation of anti-tampering devices
Maintaining records in the form of purchase/sales at various levels of supply chain
Persons brokering medicinal products are also subject to inspection by competent authorities
Persons brokering must have permanent address, contact details in the Union
Potential Targets Of EU Directive 2001/83/EC
Contd…
Repeated inspections of Manufacturers (located in the Union or in third countries) and wholesale distributors of medicinal products
Inspections of the premises of marketing authorisation holders and of brokers of medicinal products are possible
Data submitted to comply with monographs of European Pharmacopoeia
Potential Targets Of EU Directive 2001/83/EC
Current Indian Pharmaceutical Industry Status
India is a leading exporter of quality pharmaceutical products globally
Indian exporters comply with ISO, GMP/WHO GMP, ICH guidelines etc.,
Indian Drugs & Cosmetic Act terminology - Spurious drugs- Not of standard quality or substandard drugs- Adulterated drugs- Misbranded drugs
may fall under the purview with international acts
EU rules for import of API’s.
According to Articles 46b 2(b) i, ii & iiiWritten confirmation from the competent authority of the exporting third
country of the following:
The standards of good manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to those laid down by the Union.
The manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in the Union;
In the event of findings relating to non-compliance, information on such findings is supplied by the exporting third country to the Union without any delay.
Directive 2001/83/EC as amended by Directive 2011/62/EU
Implementation Of The New Directive
Concept paper submitted for public consultation.
“Implementing act on the requirements for the assessment of the regulatory framework applicable to the manufacturing of Active Substances of Medicinal products for Human Use”.
Consultation closed on March 23 , 2012.
Implementation date : July 2013
Written confirmation waived for countries to be listed as per
Article 111b.
Third country to request for “Equivalence assessment”
Assessment to be done by the commission
If assessment confirms equivalence , third country will be
included in the list.
Regular verification thereafter.
Written Confirmation & Equivalence Assessment (111b)
A review of relevant documentation
An on-site review of the third country's regulatory system, unless a mutual recognition agreement ('MRA') is in place that covers the manufacturing of active substances; and
If necessary, an observed inspection of one or more of the third country's manufacturing sites for active substances.
Equivalence Assessment
Third countries rules for GMP implementationPending the adoption of a delegated act on the principles and
guidelines of good manufacturing practice for Active Substance
EU rules to be taken into account are contained in Part II of the good manufacturing practice guideline of the EU (Eudralex Volume 4).
Country's Rules For GMP (111b(1)(a))
Article 111b(3)The Commission shall verify regularly whether the conditions of
the GMP equivalence are fulfilledThe first verification shall take place no later than three years
after the country has been included in the list.
Regular Verification
The manufacture of active substances should be subject to good
manufacturing practice regardless of whether those active substances are
manufactured in the Union or imported.
With regard to the manufacture of active substances in third countries, it
should be ensured that the legislative provisions applicable to the
manufacturing of active substances intended for export to the Union, as
well as inspections of facilities and enforcement of the applicable
provisions, provide for a level of protection of public health equivalent to
that provided for by Union law.
Minimum Expectations Of New Directive
A written confirmation that the manufacturer of the medicinal product has
verified, compliance of the manufacturer of the active substance with
principles and guidelines of good manufacturing practice by conducting
audits, in accordance with point (f) of Article 46.
The written confirmation shall contain a reference to the date of the audit
and a declaration that the outcome of the audit confirms that the
manufacturing complies with the principles and guidelines of good
manufacturing practice.
Responsibility of Formulators in the new directive
Global Bulk Drugs Imports Region Wise (Values In US$ Mn)
Sr. no Region 2008 2009 2010 YOY % %share
1 EU 14794.04 15649.54 16673.38 6.54 50.58
2 North America 7379.52 4494.00 3866.23 -13.97 11.73
3 LAC 2180.33 3338.82 3611.87 8.18 10.96
4 Asia (Excluding Middle East) 2337.40 2445.33 2611.03 6.78 7.92
5 Other European Countries 1483.95 1045.19 1680.84 60.82 5.10
6 Asean 1211.84 1250.18 1255.68 0.44 3.81
7 South Asia 1069.94 1079.49 1082.13 0.24 3.28
8 Middle East 761.60 599.14 995.23 66.11 3.02
9 Africa 420.60 423.74 450.69 6.36 1.37
10 Oceania 392.32 368.32 378.67 2.81 1.15
11 CIS 261.88 385.31 355.17 -7.82 1.08
12 Other America 4.37 5.43 6.19 14.10 0.02
World 32297.79 31084.49 32967.11 6.06
Source : UN COMTRADE
PIC/SPharmaceutical Inspection Convention (PIC)
&Pharmaceutical Inspection Co-operation
Scheme (PICS)
• PICS Established in 1995.• Current members – 40 Participating Authorities • Partners
a) EDQM European Directorate for Quality of Medicines and Health Care, Franceb) EMA- European Medicines Agencyc) UNICEFd) WHO
Requirements :- Law on medicinal products.- A GMP guide equivalent to PIC/S or EU GMP Guide.- A GMP inspectorate fulfils PIC/S quality system requirements.- Experienced GMP inspectors
Brief note on PIC/S
Objective of PIC/S
• An active and constructive co-operation in the field of GMP.• To facilitate networking between participating authorities and
to increase mutual trust, to exchange information and experience, in the field of GMP and related areas, and mutual training of GMP inspectors.
• Attain confidence of drug regulatory authority.
• Avoid duplication relating to
→ Inspections→ Licensing procedures→ Expenditure→ One time procedure
• Mutual recognition of Inspections.
• Harmonisation of GMP requirements.
• Uniform inspection systems.
• Training of inspectors.
• Exchange of information.
• Mutual confidence.
Goals of PIC/S
• PIC/S Constituted fee 8,100 CHF
• PIC/S Committee meetings – 2 per annum• Seminars - 1 per year.• Expert Circle meetings 3- per annum• Events duration are 1 to 3 days in other PIC/S
countries.• Registration fee 8100 CHF & In assessment
process, annual fee is 50% of Reg. fee for expert.
Financial Costs
PIC/S is not a trade agreement.Membership in PIC/S may facilitate the export of
pharmaceuticals.Non-PIC/S Countries (e.g. Colombia) may accept
accreditation of PIC/S participating Authorities. Consequently, the Pharmaceutical industry located in these
countries indirectly benefits PIC/S membership.
Benefits